rs753855

Positions:

• chr2-231201938-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001352754.2(ARMC9):​c.-42+3240T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 150,304 control chromosomes in the GnomAD database, including 28,535 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.59 (28535 hom., cov: 29)
• Consequence: ARMC9 NM_001352754.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

Genes affected

ARMC9 (HGNC:20730): (armadillo repeat containing 9) Predicted to be involved in cilium assembly and positive regulation of smoothened signaling pathway. Located in centriole and ciliary basal body. Implicated in Joubert syndrome 30. [provided by Alliance of Genome Resources, Apr 2022]

ARMC9 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARMC9	NM_001352754.2	c.-42+3240T>C		intron_variant		ENST00000611582.5	NP_001339683.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARMC9	ENST00000611582.5	c.-42+3240T>C		intron_variant		5	NM_001352754.2	ENSP00000484804.1

Frequencies

GnomAD3 genomes AF: 0.591 AC: 88721 AN: 150186 Hom.: 28476 Cov.: 29

Gnomad AFR AF: 0.858

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.601

Gnomad EAS AF: 0.649

Gnomad SAS AF: 0.503

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.466

Gnomad OTH AF: 0.583

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.591 AC: 88839 AN: 150304 Hom.: 28535 Cov.: 29 AF XY: 0.589 AC XY: 43168 AN XY: 73290

Gnomad4 AFR AF: 0.858

Gnomad4 AMR AF: 0.475

Gnomad4 ASJ AF: 0.601

Gnomad4 EAS AF: 0.650

Gnomad4 SAS AF: 0.501

Gnomad4 FIN AF: 0.543

Gnomad4 NFE AF: 0.466

Gnomad4 OTH AF: 0.582

Alfa AF: 0.491 Hom.: 37139

Bravo AF: 0.599

Asia WGS AF: 0.637 AC: 2215 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.9
DANN	Benign	0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs753855; hg19: chr2-232066651;